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Results for “Neuroimmunomodulation”

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At least 811 records · Page 45Linked to original sources

PubMed2002

Effect of orphanin FQ on interleukin-1beta mRNA transcripts in the rat CNS.

To elucidate the mechanism of orphanin FQ on neuroimmune modulation, the relationship between orphanin FQ and interleukin-1beta in the rat CNS in vivo and in vitro was investigated. In our experiments, it was found that orphanin FQ and interleukin-1beta mRNA transcripts showed a similar distribution in cerebral cortex, hippocampus and hypothalamus. By using the in situ hybridization technique, down-regulation of interleukin-1beta mRNA transcripts by central administration of orphanin FQ was further identified in the traumatic animal model. Similar inhibitory effects were also observed on the number of microglia in the CNS. The effects produced by orphanin FQ were abolished by combination with its receptor (OP(4))-specific antagonist [Phe(1)Psi(CH(2)-NH)Gly(2)]nociceptin-(1-13)-NH(2), which suggested that the function of orphanin FQ might be attributable to the OP(4) pathway. However, the effect on the number of astrocytes in the CNS remained unchanged, despite evidence that OP(4) is expressed on astrocytes as well as on neurons and microglia. When analyzed by reverse transcription-polymerase chain reaction, interleukin-1beta gene expression was observed to be enhanced and inhibited in primary neuron and microglial cell cultures exposed to orphanin FQ respectively. Interleukin-1beta gene expression in astrocyte cultures was not affected by treatment with orphanin FQ. Our findings suggest that the neuroimmune function of orphanin FQ might be dependent on interleukin-1beta derived from microglia, and the interaction between microglia and neurons.

Animals↗

PubMed2003

Descending pathways from the paraventricular nucleus contribute to the recruitment of brainstem nuclei following a systemic immune challenge.

Hypothalamic nuclei, particularly the paraventricular nuclei (PVN), are important brain sites responsible for central nervous system responses during an immune challenge. The brainstem catecholamine cells of the nucleus tractus solitarius (NTS) and ventrolateral medulla (VLM) have been shown to play critical roles in relaying systemic immune signals to the PVN. However, whilst it is well recognised that PVN divisions also innervate the NTS and VLM, it is not known whether descending PVN pathways can modulate the recruitment of brainstem cells during an immune challenge. Using systemic administration of the proinflammatory cytokine interleukin-1beta, in combination with Fos immunolabelling, we firstly investigated the effect of PVN lesions on NTS and VLM catecholamine and non-catecholamine cell responses. We found that ibotenic acid lesions of the PVN significantly reduced numbers of Fos-positive non-catecholamine, noradrenergic and adrenergic cells observable in the VLM and NTS after interleukin-1beta administration. We then investigated the origins of descending inputs to the VLM and NTS, activated by systemic interleukin-1beta, by mapping the distribution of Fos-positive retrogradely-labelled cells in divisions of the PVN after iontophoretically depositing choleratoxin-b subunit into the NTS or VLM one week prior to interleukin-1beta administration. We found that, after either NTS or VLM deposits, the majority of retrogradely-labelled Fos-positive cells activated by interleukin-1beta were localised in the medial and lateral parvocellular PVN divisions. Retrogradely-labelled Fos-positive cells were also observed in the NTS after VLM deposits, and in the VLM after NTS tracer deposits, suggesting reciprocal communication between these two nuclei after systemic interleukin-1beta. Thus the present study shows that the PVN has the capacity to modulate NTS and VLM responses after an immune challenge and that these may result from descending projections arising in the medial and lateral PVN divisions. These findings suggest that central nervous system responses to an immune challenge are likely to involve complex reciprocal connections between the PVN and the brainstem as well as between brainstem nuclei themselves.

Animals↗

PubMed2003

Involvement of cytokines in eating disorders: a critical review of the human literature.

A number of findings from clinical and animal studies indicate that pro-inflammatory cytokines may play roles in eating disorders. The measurement of pro-inflammatory cytokines (IL-1, IL-6, TNFalpha), which are known to decrease food intake, provides highly variable data from which firm conclusions cannot be drawn. In most of the longitudinal studies where pro-inflammatory cytokines have been shown to be impaired in anorexia or bulimia nervosa, a return to normal values was observed after renutrition. However these findings do not exclude the possibility that pro-inflammatory cytokines might be overproduced in specific brain areas and act locally without concomitantly increased serum or immune production. It was also pointed out that the production of the major type-1 cytokines (especially IL-2) was depressed in anorexia nervosa. It remains unclear whether this is due to undernutrition or to a specific underlying cause common to eating disorders. The impaired cytokine profile observed in eating disorders could be related to several factors including impaired nutrition, psychopathological and neuroendocrine factors. More particular attention should be devoted to the deregulation of the anti/pro-inflammatory balance. Deregulation of the cytokine network may be responsible for medical complications in eating disorder patients who are afflicted with chronic underweight.

Cytokines↗

PubMed2003

Inescapable shock induces resistance to the effects of dexamethasone.

Administration of bacterial endotoxin (lipopolysachharide; LPS) elevates proinflammatory cytokines, such as interleukin-1beta (IL-1beta) and IL-6, and activates the hypothalamic-pituitary-adrenal (HPA) axis. Corticosterone (CORT), the glucocorticoid (GC) effector hormone of the HPA axis in rats, inhibits both proinflammatory cytokine production/release and activity of the HPA axis itself. Exposure to chronic or repeated stressors often induces resistance to the effects of GCs. The following experiments were conducted to test the hypothesis that an acute stressor, inescapable tailshock (IS), alters responsivity of the HPA axis and proinflammatory cytokine system to dexamethasone (DEX), a synthetic GC. First, we examined the ability of various doses of DEX to suppress proinflammatory cytokine and HPA activity in response to LPS challenge 24 h after either home cage (HCC) or IS treatment. Upon finding resistance to DEX in IS animals, we examined the duration of the altered response to DEX by testing animals 1, 4 and 21 days after IS. To test whether IS animals were selectively resistant to the suppressive effects of DEX on the response to LPS, the ability of DEX to suppress HPA activity in response to a non-inflammatory stressor, exposure to an elevated "pedestal", was assessed. Again, DEX resistance was observed in IS animals. Finally, we examined whether changes in the responsivity to DEX were dependent upon the controllability of the stressor. The induction of DEX resistance was independent of the degree of behavioral control that the animal had over the stressor. Thus, a single session of IS induces DEX resistance of both HPA axis and cytokine responses measured in vivo.

Adaptation, Physiological↗

PubMed2003

Individual housing induces altered immuno-endocrine responses to psychological stress in male mice.

Social isolation and lack of social support have deleterious effects on health, thus being regarded as one of the most relevant causes of diseases in human and other mammalian species. However, only few are the studies aimed at evaluating the psychoneuroimmunological functions of individually housed subjects. The present study was designed to understand how the behavior and the physiology of male house mice might be affected by individual housing. We first analyzed whether individual housing of different duration (1-42 days) would result in immuno-endocrine dysfunction (experiment 1). Then we investigated whether housing conditions would affect the reaction to an acute mild psychological stress (experiments 2 and 3). There were three main findings: first, individually housing mice for increasing time periods did not induce any major immuno-endocrine effects compared to a stable sibling group housing. Therefore, prolonged isolation does not seem to dramatically impair mice immuno-endocrine functions. Second, when exposed to a mild acute stress, i.e. forced exposure to a novel environment, isolated mice showed higher basal corticosterone and lower type 1 (IL-2) and type 2 (IL-4) cytokines as well as splenocytes proliferation compared to group housed male mice. Finally, when faced with a free choice between a novel environment and their home cage, individually housed mice showed reduced neophobic responses resulting in increased exploration of the novel environment, thus suggesting a low anxiety profile. Altogether, our findings suggest that individual housing in itself does not change immunocompetence and corticosterone level, but does affect reactivity to a stressor. In fact, individually housed mice showed high behavioral arousal, as well as altered immuno-endocrine parameters, when challenged with mild psychological novelty-stress.

Adaptation, Physiological↗

PubMed2003

Social stress and T cell maturation in male rats: transient and persistent alterations in thymic function.

The present study demonstrates that social stress in subordinate male rats resulting from a 24-h confrontation with a dominant male opponent caused not only transient but also persistent alterations in the function and the cellular composition of the thymus. The investigation of regulation processes maintaining tissue homeostasis in the thymus showed a significant increase in apoptosis, a decrease in cellular proliferation and a decrease in thymic export as indicated by a reduction in the number of recent thymic emigrants (RTE) in the peripheral blood. The proliferative response of mature thymocytes to Concanavalin A (ConA) was also significantly reduced in socially defeated rats. Adrenalectomy (ADX) completely abolished the stress-associated alterations in thymic function whereas a decrease in total thymocyte numbers was still evident in defeated animals treated with the glucocorticoid type-II receptor antagonist RU486. The significant reduction in total thymocytes and the diminished proliferative response to ConA persisted for at least seven days after stressor cessation. An enhanced proliferative activity at this point of time may represent a beginning regeneration of thymic tissue after stress. Taken together, our studies show that social stress profoundly disturbs tissue homeostasis in the thymus and suggest that adrenal-derived hormones play a central role in mediating this effect. The strong positive relationship between total thymocyte numbers and peripheral RTE numbers and the long-lasting atrophy of the thymus in defeated animals may suggest negative consequences for the heterogeneity of naïve T cells in the peripheral T cell pool after social stress.

Adaptation, Physiological↗

PubMed2002

Does the pineal gland have a role in the psychological mechanisms involved in the progression of cancer?

Psychological factors, e.g., depression and psychological stress have been implicated in the progress of cancer. Similarly, the pineal gland and its principal secretion, melatonin, are known to influence the initiation and progress of cancer. Furthermore, changes in melatonin secretion have been linked with psychological stress and depression, and both the pineal gland and the cerebral cortex act via the limbic system in producing their effects. Both psychological stress and melatonin affect the immune system, as does the hypothalamus and the autonomic nervous system. The pineal gland has both a direct effect on cancer, and via the immune system. Psychological treatment and melatonin treatment have both been found to alleviate the course of cancer clinically. It is thus hypothesized that the pineal gland, and melatonin, are involved in the mechanism of psychological effects in the promotion of the progress of cancer.

Amygdala↗

PubMed1997

Central nervous system IL-1 beta system and neuropeptide Y mRNAs during IL-1 beta-induced anorexia in rats.

Interleukin-1 beta (IL-1 beta) induces anorexia and neuropeptide Y (NPY) increases feeding by direct action in the central nervous system (CNS). IL-1 beta, depending on the dose, attenuates or blocks NPY-induced feeding. This suggests that IL-1 beta-NPY interactions may be involved in IL-1 beta-induced anorexia. Here, RNase protection assays were used to investigate the effects of the chronic intracerebroventricular (ICV) administration of IL-1 beta (at a dose that yields estimated pathophysiological concentrations in the cerebrospinal fluid) on mRNA levels of IL-1 beta system components and NPY in the cerebellum, parietofrontal cortex, hippocampus, hypothalamus, and midbrain. The results show that the chronic ICV administration of IL-1 beta (8.0 ng/24 h for 72 h) differentially induced IL-1 beta system components across brain regions in anorectic rats. IL-1 beta mRNA and IL-1 receptor antagonist (IL-1Ra) mRNA were induced similarly, exhibiting highest and lowest expression levels in the hypothalamus and hippocampus, respectively. IL-1 receptor type I (IL-1RI) mRNA and the soluble form of IL-1 receptor accessory protein (IL-1R AcP II) mRNA were also induced in the hypothalamus and cerebellum. NPY mRNA expression showed a small, but significant decrease in the hypothalamus. Heat-inactivated IL-1 beta (8.0 ng/24 h for 72 h) had no effect on the behavioral or molecular profiles. The results suggest that endogenous upregulation of IL-1 beta contributes to IL-1 beta-induced anorexia, and that modification of NPY mechanisms also may be involved.

Animals↗

PubMed2001

Opioids, opioid receptors, and the immune response.

It is now clear that opioid receptors participate in the function of the cells of the immune system, and evidence suggests that opioids modulate both innate and acquired immune responses. We review literature here which establishes that mu-, kappa-, and delta-opioid compounds alter resistance to a variety of infectious agents, including the Human Immunodeficiency Virus (HIV). The nature of the immunomodulatory activity of the opioids has been the subject of a great deal of research over the last ten years. There is increasing evidence that effects of opioids on the immune response are mediated at several levels. Modulation of the inflammatory response appears to be a target of these compounds, including effects on phagocytic activity, as well as the response of cells to various chemoattractant molecules. Moreover, findings from several laboratories have demonstrated the impact of opioid treatment on antibody responses, and the molecular basis for this effect is likely due, at least in part, to the modulation of both cytokine and cytokine receptor expression. Future research should provide a clearer understanding of the cellular and molecular targets of opioid action within the immune system.

Antibodies, Viral↗

PubMed2001

Spontaneous remission of spasms in West syndrome--implications of viral infection.

On a database of the Japanese medical literature between 1970 and 2000, there were 29 patients with West syndrome showing spontaneous remission. In 25/29 (86%) of the patients, spontaneous remission was preceded by viral infections, among which exanthema subitum predominated. In 16/29 (55%), the spasms recurred a median of 2 months later. However, some of the remaining infants attained lasting remission of the spasms. This link between viral infections and spontaneous remission suggests immuno-inflammatory processes underlie West syndrome in certain patients. Better understanding of such mechanisms may lead to a new therapeutic approach to West syndrome.

Autoimmune Diseases↗

PubMed1999

Dehydroepiandrosterone selectively inhibits production of tumor necrosis factor alpha and interleukin-6 [correction of interlukin-6] in astrocytes.

Dehydroepiandrosterone (DHEA) is a native neurosteroid with immunomodulating activity. DHEA effectively protects animals from several viral, bacterial and parasitic infections and it was suggested that its age-associated decline is related with immunosenescence. In the present study we examined the ability of DHEA to inhibit the production of inflammatory mediators by mycoplasma-stimulated glial cells and to change the course of acute central nervous system (CNS) inflammatory disease in vivo. Addition of DHEA (10 microg/ml) markedly inhibited tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6) production (98 and 95%, respectively), whereas nitric oxide (NO) and prostaglandin E2 (PGE2) production was not affected. However, daily administration of 0.5 mg DHEA to mice or 5 mg to rats did not change the clinical outcome of experimental autoimmune encephalomyelitis (EAE).

Adjuvants, Immunologic↗

PubMed1998

Neuroimmunoregulation and natural immunity.

The development and function of the immune system is regulated by neuroendocrine factors. Immune function may be divided into adaptive and natural immunity. Adaptive immune responses are driven by specific determinants of the antigen (epitopes), require 5-10 d to fully develop, and show an accelerated or memory response after repeated exposure to the same antigen. Natural immunity may be divided into host defense mediated by non-immune factors (e.g., antimicrobial proteins, enzymes, mucus etc.) and polyspecific responses of the immune system. This polyspecific response relies on natural antibodies and on some other serum proteins (e.g., lipopolysaccharide-binding protein-LBP, C-reactive protein-CRP), and on surface receptors of macrophages, natural killer cells and B and T lymphocytes for activation. Highly conserved homologous (crossreactive) epitopes, or homotopes for short, are recognized by the natural immune system. Natural antibodies, LBP, and CRP are capable of activating the entire immune system after combination with the appropriate homotope. During febrile illness natural immune host defense is promptly elevated because of the rapid rise of natural antibodies, LBP, and CRP in the serum. This is known as the acute phase response (APR), which is initiated by a sudden rise of cytokines in the circulation, such as IL-1, IL-6, and TNF-alpha. The cytokines act on the brain, the neuroendocrine system, and on other tissues and organs, which leads to fever and profound hormonal and metabolic changes. The hypothalamus-pituitary adrenal axis is activated and serves as the primary regulator of immune and inflammatory reactions. Insulin, glucagon, and catecholeamine levels are also raised. Bone marrow activity and leukocyte function are high and the liver is converted to the rapid production of acute-phase proteins (APP). APP include LBP, CRP, fibrinogen, some complement components, enzyme inhibitors, and anti-inflammatory proteins, which may rise in the serum from several hundred to a thousand times within 24-48 hr. Therefore, natural immunity is a polyspecific response to homotopes, which functions as an instantaneous defense mechanism in health and which is rapidly boosted by cytokines and hormones during febrile illness. This is a highly successful defense reaction, as in the overwhelming majority of cases, febrile illness leads to recovery and the development of adaptive immunity in man and higher animals.

Acute-Phase Reaction↗

PubMed1998

A new theory on the common evolutionary origin of natural immunity, inflammation and stress response: the invertebrate phagocytic immunocyte as an eye-witness.

Data in favor of the hypothesis of the common evolutionary origin of natural immunity inflammation and stress response are presented. These phenomena seem to be mediated by a common pool of molecules (POMC-derived peptides, cytokines, biogenic amines, glucocorticoids, and nitric oxide). Macrophages are able to release all the above mentioned molecules. They play a primary role in defence mechanisms. Thus, we argue that this cell can be considered the eye-witness of the common evolutionary origin of the immune and neuroendocrine systems.

Animals↗

PubMed1998

Endocrine modulation of physiological responses to catabolic disease.

Disease or endotoxemia alters the plasma concentrations of anabolic hormones, particularly growth hormone (GH) and insulin-like growth-factor I (IGF-I). In general, these hormones are inhibited during the catabolic disease state. A hypothesis has evolved that anabolic hormones might be useful in patients' recovery under these and other catabolic circumstances. The treatment of cattle with GH has provided significant improvement in the physiological response of the animals to the subsequent injection of bacterial lypopolysaccharide (LPS), perhaps via inhibition of tumor necrisis factor (TNF) release. However, this improved response to disease was not observed with animals treated with GH and infected with one of two parasitic organisms, Sarcocystis cruzi or Eimeria bovis. Recent attempts with other anabolic hormones, estradiol and progesterone, have proven remarkably effective in improving the adaptive physiological responses of calves to either E. bovis infection or to the injection of LPS. All animals displayed signs of infection, but the intensity and duration of symptoms were reduced. Although a mechanism is not yet known, there were no effects on TNF; cortisol; the percentages of lymphocytes expressing CD2, 4, or 8 antigens; or the production of antibodies.

Animals↗

PubMed1998

The role of neuroendocrine immune interactions in the initiation of humoral immunity in chickens.

The presence of neuroendocrine immune interaction in mammalian species has been studied extensively and has been established. However, such an interaction is not as well established in avian species. Furthermore, the role of such an interaction in the initiation of humoral immunity is not well understood. Therefore, the present studies were conducted to determine mechanisms involved in the initiation of humoral immunity in chickens. Cornell K-strain White Leghorn immature male chickens were used for all the experiments. Changes in hormonal and leukocyte profiles after antigen stimulation were studied. The ability of different leukocytes to produce ACTH was also investigated. It was concluded that the first step in the initiation of humoral immunity after antigen exposure is the release of interleukin-1 by macrophages, which in turn stimulates the production of CRF by hypothalamus and/or leukocytes. It is important to mention that CRF production could also be a direct effect of antigen stimulation. The CRF will then stimulate ACTH production by anterior pituitary and/or leukocytes. In addition, CRF will directly enhance lymphocyte activities in the spleen. Corticosteroid production will be stimulated by ACTH and will cause redistribution of lymphocytes from circulation to secondary lymphoid organs such as the spleen for antigen processing and eventual production of antibodies against the invading antigens. Finally, both ACTH and corticosteroids will later act in a negative feedback manner to regulate and control the process of antibody production by inhibiting lymphocyte activities and/or reducing the responsiveness to different stimuli.

Adrenocorticotropic Hormone↗

PubMed1998

Neuroendocrine-immune interactions in the neonate.

Cytokine responses to lipopolysaccharides in neuroendocrine tissues are age- and tissue-dependent in neonatal pigs. Developmental differences in serum and tissue-specific responses are not necessarily equivalent. Lower levels of cytokine gene expression in neuroendocrine tissues of early neonates potentially could influence neuroendocrine and immune responses to infection. The limited information on neuroendocrine-immune responses and interactions in neonatal farm animals presents significant challenges, as well as opportunities for new discoveries and improvements of livestock production.

Acute-Phase Reaction↗

PubMed1998

The molecular basis for bidirectional communication between the immune and neuroendocrine systems.

IL-2 has analgesic effects in both central and peripheral nervous systems. There are two distinct domains in IL-2 molecule mediating immunologic and analgesic activity, respectively. The analgesic domain of IL-2 may be composed of the 44th Phe, 45th Tyr, 107th Tyr, and 117th Phe residues that are located closely in the tertiary structure of IL-2. The analgesic activity may be mediated through the analgesic domain interaction with opioid receptor. In addition to peptides, cytokines may directly bind to peptide receptors, other than their specific cytokine receptors themselves. Conversely, peptides may also interact with cytokine receptors. Thus, peptide neurotransmitters and hormones may serve as endogenous regulators of the immune system, and cytokines may also serve as neurotransmitters. Multiple actions might be mediated by interactions between distinct domains of bioactive molecules with different receptors.

Analgesics↗

PubMed1998

Regulation and role of intrapituitary IL-6 production by folliculostellate cells.

Interleukin-6, mainly produced by monocytes and macrophages is known to influence the secretion of anterior pituitary hormones and is, therefore, considered to play an important role in the interaction between the immune system and the endocrine system. However, IL-6 represents not only a lymphocyte message but is also produced within the anterior pituitary. Folliculostellate (FS) cells have been identified as the source of the intrapituitary IL-6 production in the normal pituitary, whereas in pituitary adenomas IL-6 is produced by the tumor cells themselves. The present review summarizes the knowledge about the regulation of the intrapituitary IL-6 synthesis and release in FS cells. Moreover, the possible roles of the intrinsic IL-6 production for function and growth of normal and adenomatous endocrine pituitary cells are discussed.

Adenoma↗